US4871552A - Hydantoins as animal food supplements - Google Patents
Hydantoins as animal food supplements Download PDFInfo
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- US4871552A US4871552A US07/174,651 US17465188A US4871552A US 4871552 A US4871552 A US 4871552A US 17465188 A US17465188 A US 17465188A US 4871552 A US4871552 A US 4871552A
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- hydantoin
- analogue
- hydroxy
- food composition
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- 241001465754 Metazoa Species 0.000 title claims abstract description 25
- 235000015872 dietary supplement Nutrition 0.000 title description 4
- 239000000203 mixture Substances 0.000 claims abstract description 14
- 235000018102 proteins Nutrition 0.000 claims description 26
- 108090000623 proteins and genes Proteins 0.000 claims description 26
- 102000004169 proteins and genes Human genes 0.000 claims description 26
- 235000013305 food Nutrition 0.000 claims description 18
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 12
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 11
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 6
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 5
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Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/116—Heterocyclic compounds
- A23K20/137—Heterocyclic compounds containing two hetero atoms, of which at least one is nitrogen
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S426/00—Food or edible material: processes, compositions, and products
- Y10S426/807—Poultry or ruminant feed
Definitions
- This invention relates to the field of animal nutrition.
- the invention concerns nutritive supplements for warm-blooded animals.
- Proteins are used to replace tissues, generate hormones, to provide the structural framework of the body (e.g. muscles, tendons, cartilage, etc..) and can also be consumed for energy.
- Amino acids are the building blocks of proteins. In all living organisms, proteins and their constituent amino acids are continuously metabolized and exist in a dynamic equilibrium in the cells. Approximately 20 amino acids are common constituents of animal proteins. However, eight to ten of these amino acids are essential for the animal's survival. Since the animal's reserves of these essential amino acids are normally depleted within a few hours, the animmal must replenish its supply by ingesting proteins containing appropriate amounts of essential amino acids. The nutritional value of proteins used in aminal feed is therefore a function of the presence of these essential amino acids in proper amounts. However, feeds containing proteins of low nutritional value, i.e.
- plant proteins such as wheat, corn, and soybeans are commonly fortified with L-lysine, DL-methionine and/or other essential amino acids to upgrade the nutritional value of these common animal feeds.
- KIC has special properties which distinguish it from other branched-chain ⁇ -keto acid analogues.
- KIC is the metabolic precursor of leucine, the two compounds have different metabolic fates in animals.
- KIC is absorbed mostly in the gut and utilized mostly in the liver.
- Leucine is absorbed mostly in the stomach and is metabolized in muscle tissue.
- KIC is also involved in steroid and carbohydrate metabolism.
- ⁇ -keto acid analogues as animal feed supplements possesses certain disadvantages.
- the essential amino acid L-lysine is used as a commodity feed supplement.
- the direct keto analogue of this amino acid is non-nutritional.
- KIC is degraded substantially by the rumen and thus has to be protected by coating or additives if used with ruminants.
- the branched-chain ⁇ -keto acid analogues corresponding to the essential amino acids leucine, isoleucine, and valine are unstable liquids or low-melting solids with very unpleasant odors.
- the calcium or sodium salts of the branched-chain ⁇ -keto acid analogues are the forms most commonly used as nutritive supplements. Although these salts have been shown to have the beneficial nutritive properties discussed above, they have several drawbacks: (1) bad taste; (2) unpleasant odor; (3) limited stability; and (4) degradation in the rumen. For humans, the bad taste is particularly problematic since it is difficult to mask.
- Walser has overcome this problem in some of his patents by forming the L-lysine, L-ornithine, and/or L-histidine salts of the branched-chain ⁇ -keto acid analogues.
- these salts are much more costly than simple metal salts.
- 5-Substituted hydantoins are common chemical intermediates in the manufacture of branched-chain keto acid analogues. See, e.g., U.S. Pat. No. 4,069,251. They have the same carbon structure as the branched-chain keto acid analogues. However, these hydantoins are very stable powders with little odor or taste. In addition, these precursors obviously have a lower cost than the keto acid final products. The low water solubility and stability of the hydantoins should also allow them to survive the rumen better than unprotected branched-chain keto acid analogues.
- the present invention is directed to the use of 5-alkylidene and 5-hydroxy-5-alkyl-substituted hydantoins as nutritive supplements in animal feed.
- these classes of hydantoin analogues of essential amino acids have never previously been tested or used for such purpose.
- 5-(2-methylthioethyl)-hydantoin the hydantoin analogue of the essential amino aicd DL-methionine
- Thiohydantoins i.e. a hydantoin-type structure containing a sulfur atom as part of the ring structure
- hydantoinases exist in nature that cleave urea from hydantoin rings to yield ⁇ -keto acids and amino acids. See M. Guivarch et al, Bull Soc. Chim. Fr. 1980 (1-2, Pt.2) 91-95 (CA 92: 176474); H. Yamada et al, J. Ferment. Technol. 1978 56(5), 484-91 (CA 90: 36129); U.S. Pat. No. 4,016,037; Japanese Pat. No. 70 08,633 (CA 73: 65026); H. Hasall and D.
- Hydantoins are generally metabolized in the liver via pyrimidine pathways.
- dihydrophyramidinase extracted from calf liver has been shown to act as a hydantoinase; see U.S. Pat. No. 3,964,970.
- the present invention is directed to the use of 5-alkylidene and 5-hydroxy-5-alkyl substituted hydantoin analogues of essential amino acids as a new class of nutritive supplements for warm blooded animals including poultry.
- the hydantoins conveniently are fed as additives to conventional protein-containing animal feeds. Certain embodiments of this invention are believed applicable to the attainment of particular beneficial effects and the treatment of certain disorders in animals.
- the 5-alkylidene and/or 5-hydroxy-5-alkyl hydantoins are fed to animals in nutritionally-effective amount(s), i.e., amount(s) sufficient to enhance the nutrition of the animal.
- hydantoins When the hydantoins are fed to achieve other beneficial results, or in the treatment of certain disorders, it again is an amount of such hydantoin(s) effective to produce the desired result which should be fed.
- effective amounts The determination of effective amounts is well within the skill of the artisan.
- compositions employed in the practice of the present invention comprise substituted hydantoin analogues of the essential amino acids L-valine, L-leucine, and L-isoleucine. Ingestion of these hydantoin analogues acts as a substitute for the ingestion of the analogous required essential amino acids. However, since the hydantoin analogues are absorbed and metabolized differently from the corresponding amino acids while still providing ⁇ -keto acids and amino acids for protein synthesis, special metabolic effects (beyond those produced by feeding amino acids) are obtained; these can be highly desirable and/or therapeutic.
- the present invention is directed to food compositions containing an admixture of food proteins and nutritionally-effective amounts of one or more 5-alkylidene or 5-hydroxy-5-alkyl hydantoin analogues and the use of such hydantoin analogues as food supplements to insure proper animal nutrition, promote protein sparing, and/or treat renal and liver disease.
- the present invention is also directed at the use of a hydantoin analogue supplement corresponding to leucine to lower serum, meat, milk, and egg yolk cholesterol; increase feed efficiency and growth; and enhance disease resistance. In every case, amounts sufficient to achieve the desired result should be fed/administered to the animal, such amounts being readily determined by the artisan.
- the present invention is directed to the use of one or more of the 5-alkylidene and 5-hydroxy-5-alkyl substituted hydantoin analogues of essential amino acids as nutritive supplements for animals.
- the invention comprises the use of the following hydantoin analogues:
- the hydantoin analogues can be used to fortify low quality protein feeds to provide a balanced food, or else can be used in special, therapeutic diets that provide the minimum required protein.
- the hydantoin analogues should be in an edible, nutritionally absorbable form, such as the free acid or its sodium, potassium, or calcium salt.
- VH, IH, and LH are the precursors in the manufacture of the ⁇ -keto acid analogues of, respectively, valine, isoleucine, and leucine. Both 5-alkylidene-hydantoins and 5-hydroxy-5-alkyl-hydantoins yeield the ⁇ -keto acids upon hydrolysis. Consequently, the hydantoin analogues are less costly than the corresponding -keto acid analogues.
- hydantoin analogues When used to fortify a protein-containing feed composition, hydantoin analogues can be orally administered in amounts ranging from 0.1 to 1000 milligrams (mg) per kilogram (kg) of body weight per day, the actual amount depending on the type of animal and the protein being fortified. More typically, the range is 10 to 500 mg/kg body weight/day when supplementing food that is 10 to 24% protein. These ranges correspond to 0.001-6.0 weight % of each added hydantoin analogue, based on the total dry weight of the food, or preferably 0.1-1.5% of each for large animals, such as ruminants, and 0.005-1.5% for small animals such as poultry.
- the hydantoin analogues can be orally administered in a wide variety of manners, for example blended with a compatible carrier and in solid, powder or liquid form.
- the analogues are blended with conventional protein-containing food for convenient administration.
- the branched-chain hydantoin analogues VH, IH, and LH can be substituted for the corresponding essential amino acids or ⁇ -keto acids in the diet.
- the effect of these hydantoin acids is similar to that produced by the branched chain keto acid analogues--protein sparing.
- a minimal, mixed-quality protein diet (about 400 mg. protein/kg. body weight/day, which corresponds to about 5% protein) balanced with the needed amino acids and an effective amount (e.g. 25 to 400 mg.
- each hydantoin analogue/kg body weight/day, preferably 50 to 200 mg.) substituted for the branched-chain keto acid analogue can sustain growth, produce protein sparing, and other beneficial metabolic effects.
- Such diets are known to be useful for treating wasting effects, such as malnutrition and kidney and liver disease, particularly in humans.
- LH itself can be substituted for leucine in the diet at dosages indicated above, but preferably to produce effects similar to those known to KIC.
- beneficial effects include increased growth and feed efficiency; lowered serum, meat, milk, and egg yolk cholesterol; increased milk production; increased wool production; and enhanced disease resistance.
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Abstract
Description
______________________________________ AMINO ACID α-KETO ACID ANALOGUE ______________________________________ ##STR1## ##STR2## Example: R = (CH.sub.3).sub.2 CH (isopropyl group) ##STR3## ##STR4## valine α-keto-isovaleric acid ______________________________________
______________________________________ 5-SUBSTITUTED KETO ACID HYDANTOIN AMINO ACID ANALOGUE ANALOGUE ______________________________________ ##STR5## ##STR6## ##STR7## Example ##STR8## 5-isopropylidene-hydantoin ______________________________________
TABLE I ______________________________________ Essential Amino Acid Hydantoin Analogue ______________________________________ L-valine 5-isopropylidene-hydantoin, or (VH) 5-hydroxy-5-isopropyl-hydantoin L-isoleucine 5-sec-butylidene-hydantoin, or (IH) 5-hydroxy-5-sec-butyl-hydantoin L-leucine 5-isobutylidene-hydantoin, or (LH) 5-hydroxy-5-isobutyl-hydantoin ______________________________________
Claims (15)
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US06/911,688 US4744990A (en) | 1986-09-25 | 1986-09-25 | Hydantoins as animal food supplements |
US07/174,651 US4871552A (en) | 1986-09-25 | 1988-03-29 | Hydantoins as animal food supplements |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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US5183674A (en) * | 1988-12-02 | 1993-02-02 | Thomas Olin | Food and feedstuff |
US5707837A (en) * | 1995-08-09 | 1998-01-13 | Degussa Aktiengesellschaft | Method of producing (R)-tertiary leucine |
US6358546B1 (en) * | 1999-01-15 | 2002-03-19 | Ralston Purina Company | Methods for customizing pet food |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5183674A (en) * | 1988-12-02 | 1993-02-02 | Thomas Olin | Food and feedstuff |
US5346707A (en) * | 1988-12-02 | 1994-09-13 | Thomas Olin | Food and feedstuff |
US5707837A (en) * | 1995-08-09 | 1998-01-13 | Degussa Aktiengesellschaft | Method of producing (R)-tertiary leucine |
US6358546B1 (en) * | 1999-01-15 | 2002-03-19 | Ralston Purina Company | Methods for customizing pet food |
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